Establishment of new target therapy depending on the origin of lung cancer stem cell

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461170
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kansai Medical University
• Principal Investigator: KUMANO Keiki 関西医科大学, 医学部, 准教授 (90396721)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肺がん / 幹細胞 / 系譜追跡 / Bmi1

Outline of Final Research Achievements

Alveolar stem cells were tracked by lineage tacing system. Among stem cell markers, Bmi1 expressed in the some portion of alveolar type 2(AT2) cells (SPC(+) cells). After Radiation injury, both AT2 and AT1 cells were regenerated from Bmi1(+) cells.
Mutant form of Kras (Kras G12D) caused the clonal lung cancer development from one Bmi1(+) cells. On the other hand, all mice died after mutnat Kras was expressed in the SPC(+) alveolar type 2 cells within 8weeks. In this time point, the clonal expansion of SPC(+) cells were observed but no obvious lung cancer developed. This indicate that mice were dead due to the suffocation probably by the oversecretion of surfactant proteins. These results indicate lung cancer might be originated from the Bmi1(+) cells which are some part of AT2 cells.

Free Research Field

医歯薬学